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Different expression mechanism of CYP2B subfamilies by phenobarbital and glucocorticoid hormone

Research Project

Project/Area Number 13672341
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental pharmacy
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

NEMOTO Nobuo  TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (10085631)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsCYP2B / Sex hormone / Growth hormone / Phenobarbita / シトクロムP450 / 性ホルモン
Research Abstract

The expression of Cyp2b9 and Cyp2b10 genes was investigated in kidney and liver of adult mice. The constitutive expression level of CYP2B mRNA in kidney was higher in female than in male mice, as it was in the liver where more CYP2B9 than CYP2B10 was expressed in the females, and more CYP2B10 was expressed in the males. After treatment with dexamethasone (Dex), induction of CYP2B10 in the kidneys was far greater in male than in female mice. In contrast to Dex, phenobarbital (PB), pregnenolone-16α-carbonitrile (PCN), and 1,1,1-trichloro- ,2-bis(p-chlorophenyl)eihane (DDT) did not induce the expression of the Cyp2b gene in the kidneys of either sex. In the liver, PB, PCN, and DDT induced both CYP2B9 and CYP2B10 in both sexes to the same extent, whereas Dex induced only CYP2B10 and simultaneously suppressed CYP2B9. Dex-inducible expression of CYP2B mRNA was decreased by RU-486, an antagonist of glucocor-ticoid receptor, in both the kidneys and liver from male mice. However, RU-486 itself … More induced the expression of CYP2B mRNA. Gonadectomy increased the expression of CYP2B mRNA in untreated male liver, but suppressed Dex-induced expression in the kidneys of both sexes. These observations suggest that (a) there are multiple regulatory pathways in the expression of Cyp2b genes, one of which used by Dex is mediated via the glucocorticoid receptor, which is different from that used by PB, and (b) sex hormones play a role in the regulation of the sex-dependent expression of Cyp2b genes in the mouse.
Furthermore, the constitutive expression of CYP2B mRNA in the livers of mice in the prepubertal stage was sex-independent, with CYP2B9 as the principal isoform. During the maturation stage, CYP2B10 was expressed in both sexes, whereas CYP2B9 was diminished markedly in the males, resulting in a sexually dimorphic expression in adult mice. Hypophysectomy eliminated the sexual dimorphism in the mouse CYP2B subfamily by markedly increasing the expression of both CYP2B9 and CYP2B10 in males to levels similar to those in females. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Jarukamjorn K et al.: "Sex-associated expression of the mouse hepatic and renal enzymes by glucocorticoid hormone"Biochem. Pharmacol.. 62. 161-169 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto M et al.: "Localization of estradiol-responsive region in the phenobarbital-responsive enhancer module of mouse Cyp2b10 gene"J. Biochem. Mol. Toxicol.. 15. 76-82 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyahara T et al.: "Stimulative effect of cadmium on prostaglandin E_2 production in primary mouse osteoblastic cells"Clacif. Tissue Int.. 68. 185-191 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakuma T et al.: "Different expression of hepatic renal cytochrome P450s between streptozotocin-induced diabetic mice and rats"Xenobiotica. 31. 223-237 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akiyoshi S et al.: "Targets of transcriptional regulation by transforming growth factor-β : expression profile analysis using oligonucleotide arrays"Jpn. J. Cancer Res.. 92. 257-268 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jarukamjorn K et al.: "Sexual dimorphic expression of mouse hepatic CYP2B : Alterations during development of after hypophysectomy"Biochem. Pharmacol.. 63. 2037-2041 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakuma T et al.: "Regulation of the expression of two female-predominant CYP3A mRNAs (CYP3A41 and CYP3A44) in mouse liver by sex and growth hormones"Arch. Biochem. Biophys.. 404. 234-242 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchida Y-I et al.: "Enhancer elements in the mouse Cypla2 gene for constitutive expression"Biochem. Biophys. Res. Commun.. 297. 1297-1301 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyahara T et al.: "A highly potent 26,27-hexafluoro-1α,25-dihydroxyvitamin D_3 on calcification in SV40-transformed human fetal osteoblastic cells"Calcif. Tissue Int.. 70. 488-495 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komurasaki T et al.: "Mechanism of growth promoting activity of epiregulin in primary cultures of rat hepatocytes"Growth Factors. 20. 61-69 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chida M et al.: "New allelic arrangement CYP2D6^*36x2 found in a Japanese poor metabolizer of debrisoquine"Pharmacogenetics. 12. 659-662 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ariyoshi N et al.: "Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers"Cancer Epidemiol Biomarkers Prev.. 11. 890-894 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jarukamjom K et at.: "Sex-associated expression of the mouse hepatic and renal enzymes by glucocorticoid hormone."Biochem. Pharmacol.. 62. 161-169 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto M et al.: "Localization of estradiol-responsive region in the phenobarbital-responsive enhancer module of mouse Cyp2b10 gene."J. Biochem. Mol. Toxicol.. 15. 76-82 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyahara T et al.: "Stimulative effect of cadmium on prostaglandin E_2 production in primary mouse osteoblastic cells."Clacif. Tissue Int.. 68. 185-191 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakuma T et al.: "Different expression of hepatic and renal cytochrome P450s between streptozotocin-induced diabetic mice and rats."Xenobiotica. 31. 223-237 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akiyoshi S et al.: "Targets of transcriptional regulation by transforming growth factor-β : Expression profile analysis using oligonucleotide arrays."Jpn. J. Cancer Res.. 92. 257-268 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jarukamjoru K et al.: "Sexual dimorphic expression of mouse hepatic CYP2B : Alterations during development or after hypophysectomy."Biochem. Pharmacol.. 63. 2037-2041 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakuma T et al.: "Regulation of the expression of two female-predominant CYP3A mRNAs (CYP3A41 and CYP3A44) in mouse liver by sex and growth hormones."Arch. Biochem. Biophys.. 404. 234-242 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uchida Y-I et al.: "Enhancer elements in the mouse Cypla2 gene for constitutive expression."Biochem. Biophys. Res. Commmun.. 297. 1297-1301 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyahara T et al.: "A highly potent 26,27-hexafluoro-1a,25-dihydroxyvitamin D_3 on calcification in SV40-transformed human fetal osteoblastic cells."Calcif. Tissue Int.. 70. 488-495 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komurasaki T et al.: "Mechanism of growth promoting activity of epiregulin in primary cultures of rat hepatocytes."Growth Factors. 20. 61-69 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chida M et al.: "New allelic arrangement CYP2D6^*36x2 found in a Japanese poor metabolizer of debrisoquine."Pharmacogenetics. 12. 659-662 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ariyoshi N et al.: "Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers."Cancer Epidemiol Biomarkers Prev.. 11. 890-894 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jarakamjorn K et al.: "Sexual dimorphic expression of mouse hepatic CYP2B : Alterations during development or after hypophysectomy"Biochem. Pharmacol.. 63. 2037-2041 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sakuma T et al.: "Regulation of the expression of two female-predominant CYP3A mRNAs (CYP3A41 and CYP3A44) in mouse liver by sex and growth hormones"Arch. Biochem. Biophys.. 404. 234-242 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uchida Y-I et al.: "Enhancer elements in the mouse Cypla2 gene for constitutive expression"Biochem. Biophys. Res. Commun.. 297. 1297-1301 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Komurasaki T et al.: "Mechanism of growth promoting activity of epiregulin in primary cultures of rat hepatocytes"Growth Factors. 20. 61-69 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chida M et al.: "New allelic arrangement CYP2D6^*36x2 found in a Japanese poor metabolizer of debrisoquine"Pharmacogenetics. 12. 659-662 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ariyoshi N et al.: "Genetic polymorphism of CYP2A6 gene and tobacco-induced lung cancer risk in male smokers"Cancer Epidemiol Biomarkers Prev.. 11. 890-894 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Jarukamjorn K, Sakuma T, Yamamoto M, Ohara A, Nemoto N.: "Sex-associated expression of mouse hepatic and renal CYP2B enzymes by glucocorticoid hormones"Biochem Pharmacol. 62. 161-169 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakuma T, Honma R, Maguchi S, Tamaki H, Nemoto N.: "Different expression of hepatic and renal cytochrome P450s between the streptozotocin-induced diabetic mouse and rat"Xenobiotica. 31. 223-237 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto M, Sakuma T, Ichimaru H, Nemoto N.: "Localization of estradiol-responsive region in the phenobarbital-responsive enhancer module of mouse Cyp2b-10 gene"J Biochem Mol Toxicol. 15. 76-83 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akiyoshi S, Ishii M, Nemoto N, Kawabata M, Aburatani H, Miyazono K.: "Targets of transcriptional regulation by transforming growth factor-beta : expression profile analysis using oligonucleotide arrays"Jpn J Cancer Res. 92. 257-268 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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